Reduced expression ofβ-catenin inhibitor Chibby in colon carcinoma cell lines
Reduced expression ofβ-catenin inhibitor Chibby in colon carcinoma cell lines作者机构:Institute of Pathology University of RegensburgFranz-Josef-Strauss-Alice 1193053 RegensburgGermany Department of Pharmacology BST 7-168Stony BrookNY 11794-8651United States Institute of Pathology University of RegensburgFranz-Josef-Strauss-Allee 1193053 RegensburgGermany
出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))
年 卷 期:2006年第12卷第10期
页 面:1529-1535页
核心收录:
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金:Supported by grants from the DFG and the Deutsche Krebshilfe to A.B
主 题:Chibby Wnt β-catenin Colorectal carcinoma Colon carcinoma cell lines
摘 要:AIM: To analyse the Chibby expression and its function in colon carcinoma cell lines and colorectal carcinoma (CRC). METHODS: Chibby expression levels were investigated by quantitative RT-PCR in a panel of seven different colon carcinoma cell lines. By sequencing, we analysed mutational status of Chibby. To test whether Chibby exhibited effects on β-catenin signalling in colon carcinoma cells, we transfected SW480 cells with Chibby expression plasmid and, subsequently, analysed activity of β-catenin and tested for alterations in cellular phenotype. In addition, we examined Chibby mRNA levels in samples of colorectal carcinomas and adjacent normal tissues by using quantitative RT-PCR and hybridised gene chips with samples from CRC and normal tissues. RESULTS: Chibby mRNA expression was strongly downregulated in colon carcinoma cell lines in comparison to normal colon epithelial cells and no mutation in any of the examined colon carcinoma cell lines was found. Further, we could show that Chibby inhibited β-catenin activity in TOPflash assays when over-expressed in SW480 cells. Proliferation and invasion assays with Chibby transfected SW480 cells did not reveal profound differences compared to control cells. In contrast to these in vitro data, quantitative RT-PCR analyses of Chibby mRNA levels in CRC tumor samples did not show significant differences to specimens in adjacent non-cancerous tissue. Consistent with these findings, gene chips analysing tissue samples of tumors and corresponding normal tissue did not show altered Chibby expression CONCLUSION: Altered Chibby expression might be observed in vitro in different colon carcinoma cell lines. However, this finding could not be confirmed in vitro in CRC tumors, indicating that Chibby is not likely to promote CRC tumor development or progression. As Chibby is an important inhibitor of β-catenin signalling, our data implicate that the usability of colon carcinoma cell lines for in vitro studies analysing the Wnt/β-ca